Continuous measurement of neurotransmitters in brain tissue is now possible using electrochemical sensor technology. More recent development by our group, under sponsorship of an NIMH funded grant, has led to the development of an integrated carbon microsensor array capable of mapping the spatial and temporal distribution of neuronal messengers such as nitric oxide (NO) and dopamine. This proposal builds on our previous grant, and addresses the design of an intimate integrated electrochemical sensor and electronic interface in the form of a very large scale integrated (VLSI) chip to make multi-sensor measurement of neurotransmitter activity feasible. The rationale behind this technology development is to a) facilitate measurement of neurotransmitters in pathology in ischemic injury, and b) extreme miniaturization and high integration for in vitro and in vivo studies. The present proposal brings together several innovative design solutions: 1) Cooperative design of the novel microsensor array with an integrated VLSI circuitry presented here. 2) Integrated circuit with several unique features: a) Silicon-on-sapphire substrate technology for very low leakage currents and implementing mixed sensor and analog electronic circuitry, b) Current mode design for very low current, low-noise circuit, and c) Sigma-delta analog-to-digital conversion for high resolution serial digitization and signal transmission (which would eventually facilitate telemetry). This integrated microsensor array/VLSI system will be tested a) in vitro: in a hippocampal brain slice preparation to obtain high-resolution measurements of the neurotransmitter release and distribution, and b) in vivo: in acute rodent model of ischemic brain injury. In our research, this technology will help elucidate the role of neurochemicals in brain slice and in vivo ischemic models. A proof of concept demonstration in brain slice and acute rodent models will set the stage for chronically implanted in vivo animal chronic studies where the fully integrated solution will find the most exciting eventual use.